Cucurbitacin B reverses multidrug resistance by targeting CIP2A to reactivate protein phosphatase 2A in MCF-7/Adriamycin cells
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in various tumors. A previous study found that CIP2A expression is associated with doxorubicin (Dox) resistance. In the present study, we investigated whether cucurbitacin B (CuB), a natural anticancer...
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| Veröffentlicht in: | Oncology reports 2016-08, Vol.36 (2), p.1180-1186 |
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| creator | Cai, Fen Zhang, Liang Xiao, Xiangling Duan, Chao Huang, Qiuyue Fan, Chunsheng Li, Jian Liu, Xuewen Li, Shan Liu, Ying |
| description | Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in various tumors. A previous study found that CIP2A expression is associated with doxorubicin (Dox) resistance. In the present study, we investigated whether cucurbitacin B (CuB), a natural anticancer compound found in Cucurbitaceae, reversed multidrug resistance (MDR) and downregulated CIP2A expression in MCF-7/Adriamycin (MCF-7/Adr) cells, a human breast multidrug-resistant cancer cell line. CuB treatment significantly suppressed MCF-7/Adr cell proliferation, and reversed Dox resistance. CuB treatment also induced caspase-dependent apoptosis, decreased phosphorylation of Akt (pAkt). The suppression of pAkt was mediated through CuB-induced activation of protein phosphatase 2A (PP2A). Furthermore, CuB activated PP2A through the suppression of CIP2A. Silencing CIP2A enhanced CuB-induced growth inhibition, apoptosis and MDR inhibition in MCF-7/Adr cells. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A promotes the reversal of MDR induced by CuB. |
| doi_str_mv | 10.3892/or.2016.4892 |
| format | Article |
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A previous study found that CIP2A expression is associated with doxorubicin (Dox) resistance. In the present study, we investigated whether cucurbitacin B (CuB), a natural anticancer compound found in Cucurbitaceae, reversed multidrug resistance (MDR) and downregulated CIP2A expression in MCF-7/Adriamycin (MCF-7/Adr) cells, a human breast multidrug-resistant cancer cell line. CuB treatment significantly suppressed MCF-7/Adr cell proliferation, and reversed Dox resistance. CuB treatment also induced caspase-dependent apoptosis, decreased phosphorylation of Akt (pAkt). The suppression of pAkt was mediated through CuB-induced activation of protein phosphatase 2A (PP2A). Furthermore, CuB activated PP2A through the suppression of CIP2A. Silencing CIP2A enhanced CuB-induced growth inhibition, apoptosis and MDR inhibition in MCF-7/Adr cells. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A promotes the reversal of MDR induced by CuB.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2016.4892</identifier><identifier>PMID: 27350399</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Autoantigens - metabolism ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Cancer therapies ; Caspases - metabolism ; Cell cycle ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Chemotherapy ; CIP2A ; Cucurbitaceae - chemistry ; cucurbitacin B ; Cytotoxicity ; Down-Regulation - drug effects ; Doxorubicin - pharmacology ; Drug resistance ; Drug Resistance, Multiple - drug effects ; Female ; Gene Expression Regulation, Neoplastic - drug effects ; Genetic aspects ; Health aspects ; Humans ; Kinases ; Leukemia ; MCF-7 Cells ; Membrane Proteins - metabolism ; multi-drug resistance ; Multidrug resistant organisms ; Oncogenes ; Phosphatase ; Phosphatases ; Phosphorylation - drug effects ; Plant products ; PP2A ; Properties ; Protein Phosphatase 2 - metabolism ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Studies ; Triterpenes - pharmacology</subject><ispartof>Oncology reports, 2016-08, Vol.36 (2), p.1180-1186</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-b7a4e311cfc603da83f9ebaaf075af5351b6500dbd6ff6fd09b2560bf43963f13</citedby><cites>FETCH-LOGICAL-c486t-b7a4e311cfc603da83f9ebaaf075af5351b6500dbd6ff6fd09b2560bf43963f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27925,27926</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27350399$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Fen</creatorcontrib><creatorcontrib>Zhang, Liang</creatorcontrib><creatorcontrib>Xiao, Xiangling</creatorcontrib><creatorcontrib>Duan, Chao</creatorcontrib><creatorcontrib>Huang, Qiuyue</creatorcontrib><creatorcontrib>Fan, Chunsheng</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><creatorcontrib>Liu, Xuewen</creatorcontrib><creatorcontrib>Li, Shan</creatorcontrib><creatorcontrib>Liu, Ying</creatorcontrib><title>Cucurbitacin B reverses multidrug resistance by targeting CIP2A to reactivate protein phosphatase 2A in MCF-7/Adriamycin cells</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in various tumors. A previous study found that CIP2A expression is associated with doxorubicin (Dox) resistance. In the present study, we investigated whether cucurbitacin B (CuB), a natural anticancer compound found in Cucurbitaceae, reversed multidrug resistance (MDR) and downregulated CIP2A expression in MCF-7/Adriamycin (MCF-7/Adr) cells, a human breast multidrug-resistant cancer cell line. CuB treatment significantly suppressed MCF-7/Adr cell proliferation, and reversed Dox resistance. CuB treatment also induced caspase-dependent apoptosis, decreased phosphorylation of Akt (pAkt). The suppression of pAkt was mediated through CuB-induced activation of protein phosphatase 2A (PP2A). Furthermore, CuB activated PP2A through the suppression of CIP2A. Silencing CIP2A enhanced CuB-induced growth inhibition, apoptosis and MDR inhibition in MCF-7/Adr cells. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A promotes the reversal of MDR induced by CuB.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Autoantigens - metabolism</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cancer therapies</subject><subject>Caspases - metabolism</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemotherapy</subject><subject>CIP2A</subject><subject>Cucurbitaceae - chemistry</subject><subject>cucurbitacin B</subject><subject>Cytotoxicity</subject><subject>Down-Regulation - drug effects</subject><subject>Doxorubicin - pharmacology</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple - drug effects</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>MCF-7 Cells</subject><subject>Membrane Proteins - metabolism</subject><subject>multi-drug resistance</subject><subject>Multidrug resistant organisms</subject><subject>Oncogenes</subject><subject>Phosphatase</subject><subject>Phosphatases</subject><subject>Phosphorylation - drug effects</subject><subject>Plant products</subject><subject>PP2A</subject><subject>Properties</subject><subject>Protein Phosphatase 2 - metabolism</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Studies</subject><subject>Triterpenes - pharmacology</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptks1rFTEUxQdRbK3uXMuAIF04r_mYZCbL59BqoaILBXchk9y8lzIzGZNM4W38283Q2lqRLJJcfvfck3CK4jVGG9oKcubDhiDMN3W-PCmOcSNwRWqKn-YzIriilP04Kl7EeI0QaRAXz4sj0lCGqBDHxa9u0UvoXVLaTeWHMsANhAixHJchOROWXS5FF5OaNJT9oUwq7CC5aVd2l1_Jtkw-A0ond6MSlHPwCbLQvPdx3qukIpQZypXP3UXVnG1NcGo8rLM0DEN8WTyzaojw6m4_Kb5fnH_rPlVXXz5edturStctT1XfqBooxtpqjqhRLbUCeqUsapiyjDLcc4aQ6Q23lluDRE8YR72tqeDUYnpSnN7qZoM_F4hJji6uDtQEfokStwjXpOFsRd_-g177JUzZncSCEi5oHvpA7dQA0k3Wp6D0Kiq3NROctUQ0mdr8h8rLwOi0n8C6XH_U8O6vhj2oIe2jH5bk_BQfg-9vQR18jAGsnIMbVThIjOSaC-mDXHMh11xk_M3do5Z-BHMP_wnCw-A4q8k44-M940NFeYVIhfMv0d-CyL3s</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>Cai, Fen</creator><creator>Zhang, Liang</creator><creator>Xiao, Xiangling</creator><creator>Duan, Chao</creator><creator>Huang, Qiuyue</creator><creator>Fan, Chunsheng</creator><creator>Li, Jian</creator><creator>Liu, Xuewen</creator><creator>Li, Shan</creator><creator>Liu, Ying</creator><general>D.A. 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A previous study found that CIP2A expression is associated with doxorubicin (Dox) resistance. In the present study, we investigated whether cucurbitacin B (CuB), a natural anticancer compound found in Cucurbitaceae, reversed multidrug resistance (MDR) and downregulated CIP2A expression in MCF-7/Adriamycin (MCF-7/Adr) cells, a human breast multidrug-resistant cancer cell line. CuB treatment significantly suppressed MCF-7/Adr cell proliferation, and reversed Dox resistance. CuB treatment also induced caspase-dependent apoptosis, decreased phosphorylation of Akt (pAkt). The suppression of pAkt was mediated through CuB-induced activation of protein phosphatase 2A (PP2A). Furthermore, CuB activated PP2A through the suppression of CIP2A. Silencing CIP2A enhanced CuB-induced growth inhibition, apoptosis and MDR inhibition in MCF-7/Adr cells. In conclusion, we found that enhancement of PP2A activity by inhibition of CIP2A promotes the reversal of MDR induced by CuB.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>27350399</pmid><doi>10.3892/or.2016.4892</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Autoantigens - metabolism Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Cancer therapies Caspases - metabolism Cell cycle Cell Line, Tumor Cell Proliferation - drug effects Chemotherapy CIP2A Cucurbitaceae - chemistry cucurbitacin B Cytotoxicity Down-Regulation - drug effects Doxorubicin - pharmacology Drug resistance Drug Resistance, Multiple - drug effects Female Gene Expression Regulation, Neoplastic - drug effects Genetic aspects Health aspects Humans Kinases Leukemia MCF-7 Cells Membrane Proteins - metabolism multi-drug resistance Multidrug resistant organisms Oncogenes Phosphatase Phosphatases Phosphorylation - drug effects Plant products PP2A Properties Protein Phosphatase 2 - metabolism Proteins Proto-Oncogene Proteins c-akt - metabolism Studies Triterpenes - pharmacology |
| title | Cucurbitacin B reverses multidrug resistance by targeting CIP2A to reactivate protein phosphatase 2A in MCF-7/Adriamycin cells |
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